1. The major current focus of this project is a randomized, multicenter, double-blind, placebo-controlled Phase III study to evaluate the effect of valaciclovir in preventing the transmission of herpes simplex virus (HSV) in heterosexual couples discordant for the presence of herpes simplex type 2 virus (HSV-2) antibody. The seropositive source partner is randomized to receive valaciclovir 500 mg once daily or placebo for 8 months, and the susceptible seronegative partner is monitored for clinical and subclinical (serological) acquisition of HSV. A total of 1500 couples will be randomized into the study, at approximately 35 outpatient centers in the United States, Canada and Europe. This study is open for accrual and at this point, 22 couples have been randomized at the NIH site. 2. HSV 863 is a human monoclonal antibody against herpes simplex virus. In vitro and in vivo studies showed that HSV 863 is effective both prophylactically and therapeutically against herpes simplex viruses. In a second study being designed now, we plan to assess the safety, potency and pharmacokinetics of HSV 863 preparation in an adult population before it is tested as adjunct therapy for neonatal herpes. This study will be followed by a phase I/II study of HSV 863 in babies with encephalitis and disseminated neonatal HSV infection to further determine the dose to be used in a phase III controlled trial for babies with neonatal HSV infection. The clinical research protocol has been developed, and the study is waiting for the production of the monoclonal antibody at the Biological Resources Branch at the National Cancer Institute facility in Frederick, Maryland. - Herpes simplex virus, STD, prevention, antiviral, monoclonal antibody, neonatal, central nervous system - Human Subjects